Process for brominating a sulfo acetamide

ABSTRACT

Brominated sulfoacetic acid amides of the formula

United States Patent Goralski 5] Nov. 11, 1975 PROCESS FOR BROMINATING ASULFO [56] References Cited ACETAMIDE FOREIGN PATENTS OR APPLICATIONS[75] Inventor: Christian T. Goralski, Midland. t.472.31() 3/1967 FrunccMich. [731 Assignecz The Dow Chemical Company PHI-"(HT E amu erR|chardJ; Gallagher Midland Mich ASSISIGH! brammer-lose Tovar Attorney, Agent,or Fl'rmTheodore Post; C 4 Kenneth {22] Filed: Sept. 3, 1974 Bjork [2i]Appl, No.1 502,708

RI edUS A l D [57] ABSTRACT e at pp canon am Brominated sulfoacetic acidamides of the formula {62} Division of Ser, No. 330,6l3, Feb, 8, 1973.Pat. No.

3.861935. R,R,NC0CBr H -,s0,NR.R

in which R and R are independently selected from [52] U5. Cl.260/246 B;260/247.l R; 260/247.l M; hydrogen and lower alkyl or, in conjunctionwith the 260/29363; 260/293.7l; Nil/293 85; itrogen atom, form aheterocycle which may Contain 260/326.42; 260/3265 SF; n oxygen heteroatom and x is an integer from I to 2. 260/556 A; 260/ The compounds areprepared by brominating amides [Sl] Int. Cl.'. C07D 295/[8 f Suhbaceticadd The: Compounds have antimim-(y [58] Field of Search i. 260/2916},246 B, 556 A,

260/3265 SF. 326.42, 293.85, 247.] R, 247.! M, 293.71

bial activity 1 Claim. N0 Drawings PROCESS FOR BROMINATING A SULFOACETAMIDE SUMMARY OF THE lNVENTlON This is a division, of applicationSer. No. 330,612 filed Feb. 8, 1973 now US. Pat. No. 3,862,935 issued1/28/75.

This invention concerns brominated sulfoacetic acid amides representedby the formula wherein R and R are independently selected from hydrogenand lower alkyl or, in conjunction with the nitrogen atom, form aheterocycle which may also contain an oxygen hetero atom and may besubstituted with l to 2 lower alkyl groups, such as, for example, apyrrolidino, piperidino, morpholino, 4-methylpiperidino or2,6-dimethylmorpholino group and x rep resents an integer from 1 to 2.in the specification and claims, lower alkyl designates a 1 to 4 carbonatom straight or branched-chain alkyl group, i.e., from 1, to 2, to 3,to 4 carbon atoms, such as, for example, methyl, ethyl, propyl,isopropyl, butyl, isobutyl or secondary butyl.

The compounds are prepared by brominating amides of sulfoacetic acid inaqueous medium with bromine in the presence of hydrobromic acid. Whenmonobrominated amide is desired, substantially equimolar proportions ofsulfoacetic acid amide and bromine are used, and when the dibrominatedamides are desired, a substantial excess of more than 2 molarproportions up to about 5 molar proportions of bromine per molarproportion of sulfoacetic acid amide is used. The reaction isadvantageously carried out at room temperature. The compounds haveantimicrobial activity.

DESCRIPTION OF SOME PREFERRED EMBODIMENTS The following examplesdescribe representative specific embodiments and the best modecontemplated by the inventor of carrying out the invention. Thecompounds are identified by elemental analysis and/or nuclear magneticresonance spectroscopy.

EXAMPLE 1 l Bromo( piperidinosulfonyhacetyl )piperidine In a 250 ml.single-neck flask equipped with a magnetic stirrer place 1.37 g. (0.005mol) of 1- (piperidinosulfonyl)acetyl)piperidine, 150 ml. of water, 2.0ml. of 48% hydrobromic acid and 0.80 g. (0.005 mol) of bromine. Themixture is not homogenous; a portion of both the amide and the bromineare not in solution. The flask is stoppered and the mixture is allowedto stir at room temperature. After a period of 8 days, the bromine colordisappears and a white precipitate forms. The precipitate is filteredoff, air-dried and recrystallized from approximately 20 ml. of absoluteethanol to give 0.70 g. of l-(bromo( piperidinosulfonyl)acetyl)piperidine, m.p. l 16-118C.

Anal. Calcd. for C H BrN O S: C, 40.79; H, 5.99; Br, 22.62; N, 7.93; S,9.07. Found: C, 40.39; H, 5.90; Br, 23.40; N, 7.56; S, 8.81.

EXAMPLE 2 4-( Bromo(morpholinosulfonyl )acetyl )morpholine [n a 500 ml.flask equipped with a magnetic stirrer place 5.56 g. (0.02 mol) of4-(morpholinosulfonyl- )acetyl)morpholine, 300 ml. of water, 2.5 ml. of48% hydrobromic acid and 3.20 g. (0.02 mol) of bromine. The flask isstoppered and the mixture is allowed to stir at room temperature. After9 days, the bromine color disappears and a fluffy, white precipitateforms. The solid is filtered, washed with water, air-dried, andrecrystallized from approximately ml. of absolute ethanol to give 3.98g. of 4-(bromo(morpholinosulfonyl- )acetyl)morpholine, m.p. 184-1 C.

Anal. Calcd. for C H BrN O S: C, 33.63; H, 4.80; Br, 22.37; N, 7.84; S,8.98. Found: C, 34.03; H, 4.85; Br, 22.40; N, 7.94; S, 8.97.

EXAMPLE 3 2,2-Dibromo-2-(sulfamoyl )acetamide In a 500 ml. three-neckflask equipped with a magnetic stirrer and an addition funnel place 5.0g. (0.036 mol) of sulfamoylacetamide, 360 ml. of water, and 18 ml. of48% hydrobromic acid. To this solution, 17.39 g. (0.108 mol) of bromineis added dropwise with stirring. After the addition is complete, thereaction mixture is allowed to stir at room temperature for 70 hours.The water is removed in vacuo from the aqueous layer, leaving a thick,tan liquid. A small amount of ethanol is added to the liquid, and theresulting solution is cooled in an ice bath. A white solid separateswhich is filtered, air-dried, and recrystallized from ether/hexane togive 0.62 g. of 2,2-dibromo-2-(sulfamoyl)acetamide as whitemicrocrystals, m.p. 232-234C.

Anal. Calcd. for C H Br N O S: C, 8.12; H, 1.36; Br, 5400; N, 9.47; S,10.83. Found: C, 8.57; H, 1.67; Br, 53.70; N, 9.55; S, 10.84.

EXAMPLE 4 2-Bromo-2-(dimethylsulfamoyl)-N,N-dimethylacetamide Theprocedure of Example 3 is repeated, substituting 2-( dimethylsulfamoylN,N-dimethylacetamide in place of sulfamoylacetamide and reducing theamount of bromine to 0.036 mol. The yellow crystalline product obtainedmelts at 58-61C.

The compounds of the invention are employed as antimicrobials for thecontrol of bacteria, fungi and yeasts. For such uses, the compounds canbe employed in an unmodified form or dispersed on a finely divided solidand employed as dusts. Such mixtures can also be dispersed in water withor without the aid of a surfaceactive agent and the resulting aqueoussuspensions employed as sprays. in other procedures, the products can beemployed as active constituents in solvent solutions, oil-in-water orwater-in-oil emulsions or aqueous dispersions. The augmentedcompositions are adapted to be formulated as concentrates andsubsequently diluted with additional liquid or solid adjuvants toproduce the ultimate treating compositions. Good results are obtainedwhen employing compositions containing antimicrobial concentrations andusually from about to 10,000 parts by weight of one or more of thecompounds per million parts of such composition.

In representative operations, compounds of the present invention weretested for their activity as antimicro- 3,919,213 3 4 bials usingconventional agar dilution tests. The followbrominating an amide ofsulfoacetic acid correspond ing Table presents results, expressed asconcentration ing to the formula of toxicant in parts per million toachieve lOO% growth inhibition (kills) of the indicated organisms.

Minimum (irouth Inhibitory Concentration. ppm

C ompound of Example Sa Ca St Mp Tm Bs Cp Aa Pp Cf Ci Ts A! Rn 500 500500 lOO 100 100 500 500 I 500 500 100 580 500 500 500 500 I00 SUU 500500 500 500 I00 3 I00 I00 lU'U l (X) l ()U 100 H1O l 00 l ()0 l ()0 l[)0 100 100 500 4 I00 H 100 I00 l() 100 2 I00 l0 l0(] 2 2 2 2 Sa S.aureus Cu C albicans St S. typhus-a Mp M phlei Tm T. mentugrophytes B5B. subtilis Cp C. pelliculosa Au A aerogenes Pp P. pullulans Cf Cfragans Ci C. ips T5 Trichoderm Sp. Madison P-42 At A. terreus Rn R.nigricuns 50 growth inhibition nu control at 500 ppm 2 no control at I00ppm The sulfoacetic acid amlde starting materials are prepared by themethod of Hoogenboom e.a., J. Org. Chem. 34, 3414 (1969).

What is claimed is:

l. A method for preparing a brominated amide of sulfoacetic acidcorresponding to the formula wherein R, and R are independently selectedfrom hydrogen and lower alkyl or, in conjunction with the nitrogen atom,form pyrrolidino, piperidino, morpholino, 4-methyl piperidino or2,6-dimethyl morpholino, and x is an integer from I to 2, whichcomprises the step of wherein R and R have the meaning previously givenby mixing in the presence of aqueous hydrobromic acid as reaction mediumsubstantially equimolar proportions of bromine and a said sulfoaceticacid amide corresponding to the last formula to obtain a monobrominatedsulfoacetic acid amide, and mixing in excess of 2 molar proportions upto about 5 molar proportions of bromine per molar proportion of theindicated sulfoacetic acid amide to obtain a dibrominated sulfoaceticacid amide and recovering the said brominated sulfoacetic acid amide.

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTIONPATENT NO. 3 919 2 1 of 2 DATED 1 November ll, 1975 lNVENT 1 ChristianT. Goralski It is certified that error appears in the above-identifiedpatent and that said Letters Patent are hereby corrected as shown below;

Column 1, line 54, (piperidinosulfonyl)" should read-((piperidinosulfonyl)--;

Column 1, line 65, "ll6-ll8C" should read -ll6-ll8C";

Column 2, line 5, "4-(morpholinosulfonyl" should read4((morpholinosulfonyl- Column 2, line 15, "l84l85C" should read-l84-l85C-;

Column 2, line 35, "232-234C" should read --232234C--;

Column 2, line 48, "SS-61C" should read -586lC-;

Columns 3 and 4, in the Table, under the first heading titled "Compoundof Example", the first blank should read -l;

Columns 3 and 4, in the Table, under the first heading titled "Compoundof Example", "500" should read -2;

Columns 3 and 4, in the Table, under the heading titled "Cp", line 4,"2" should read 2 Columns 3 and 4, in the Table, under the headingtitled "Ci", line 4, "2" should read -2 Columns 3 and 4, in the Table,under the heading titled "Ts", line 2, the blank should read 500--;

Columns 3 and 4, in the Table, under the heading titled "Ts", line 4,"2" should read 2 UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATEOF CORRECTION PATENT NO. l3r9l9,2l3 Z of 2 DATED I November 11, 1975INVENTOR S 1 Christian T. Goralski It is cerhhed theL error appears inthe above-identified patent and that said Letters Patent are herebycorrected as shown heiow:

in the Table, under the heading titled "500" should read l00-;

Columns 3 and 4,

"At", line 2,

Columns 3 and 4, in the Table, under the heading titled "At", line 4,"2" should read 2 Columns 3 and 4, in the Table, under the headingtitled "Rn", line 2, "100" should read 500;

Columns 3 and 4, in the Table, under the heading titled "Rn", line 4,"2" should read 2 Columns 3 and 4, in the Table, in the last footnote,

"2" should read 2 Signed and Scaled this A Most.

RUTH c. msori AIM-fling ARSHALL DANN ummmmm-r ujlan'ms and Trademarks

1. METHOD FOR PREPARING A BROMINATED AMIDE OF SULFOACETIC ACIDCORRESPONDING TO THE FORMULA